Technical Field
The present invention relates to a flow cell for both batch and continuous simultaneous electrochemical and electron paramagnetic resonance spectroscopic measurements, and methods of using the flow cell.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present invention.
New U.S. FDA guidelines on Metabolites in Safety Testing (MIST) have led pharmaceutical companies to reassess the timing of drug metabolite studies within the development process. To facilitate effective decision making, information on metabolite identity, quantity, pharmacological, and toxicological effects is now often required at earlier stages. Oxidation is a primary route of drug metabolism, and can result in the production of reactive species that may lead to adverse effects. Studies have shown that electrochemical (EC) oxidation can be used to produce species that correspond to biological oxidative metabolites.
Electron paramagnetic resonance (EPR) spectroscopy yields incontrovertible evidence of the presence of paramagnetic intermediates (e.g. radicals) formed in oxidation processes. In addition, EPR spectroscopy sheds light on the molecular structure near the unpaired electron. Therefore, this technique may be employed to identify the paramagnetic species and help researchers elucidate the oxidation mechanism that leads biological oxidative metabolites.
A simultaneous EC-EPR technique was developed more than fifty years ago to identify paramagnetic intermediates in EC reactions (D. H. Geske, A. H. Maki, Journal of the American Chemical Society, 1960, 82, p. 2671; J. D. Wadhawan, R. G. Compton Encyclopedia of Electrochemistry, 2003, vol. 2, Wiley VCH, Germany, p. 171—each incorporated herein by reference in its entirety). A variety of EC-EPR cells have been designed to facilitate this technique (R. N. Bagchi, A. M. Bond, F. Scholz, Electroanalysis, 1.989, 1, p. 1—incorporated herein by reference in its entirety). However, these cells are either expensive or difficult to use, and the electrodes in these cells are made of platinum or silver precious metals. In addition, these cells are designed for batch monitoring and hence are incompatible with continuous measurements.
In view of the foregoing, the objective of the present disclosure is to provide an economical flow cell for batch and continuous simultaneous EC and EPR measurements.